McMaster University

About: McMaster University is a education organization based out in Hamilton, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 41361 authors who have published 101269 publications receiving 4251422 citations.

Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease.

Abstract: Brain-derived neurotrophic factor (BDNF) is critical for the function and survival of neurons that degenerate in the late stage of Alzheimer's disease (AD). There are two forms of BDNF, the BDNF precursor (proBDNF) and mature BDNF, in human brain. Previous studies have shown that BDNF mRNA and protein, including proBDNF, are dramatically decreased in end-stage AD brain. To determine whether this BDNF decrease is an early or late event during the progression of cognitive decline, we used western blotting to measure the relative amounts of BDNF proteins in the parietal cortex of subjects clinically classified with no cognitive impairment (NCI), mild cognitive impairment (MCI) or mild to moderate AD. We found that the amount of proBDNF decreased 21 and 30% in MCI and AD groups, respectively, as compared with NCI, consistent with our previous results of a 40% decrease in end-stage AD. Mature BDNF was reduced 34 and 62% in MCI and AD groups, respectively. Thus, the decrease in mature BDNF and proBDNF precedes the decline in choline acetyltransferase activity which occurs later in AD. Both proBDNF and mature BDNF levels were positively correlated with cognitive measures such as the Global Cognitive Score and the Mini Mental State Examination score. These results demonstrate that the reduction of both forms of BDNF occurs early in the course of AD and correlates with loss of cognitive function, suggesting that proBDNF and BDNF play a role in synaptic loss and cellular dysfunction underlying cognitive impairment in AD.

Protein Phylogenies and Signature Sequences: A Reappraisal of Evolutionary Relationships among Archaebacteria, Eubacteria, and Eukaryotes

Abstract: The presence of shared conserved insertion or deletions (indels) in protein sequences is a special type of signature sequence that shows considerable promise for phylogenetic inference. An alternative model of microbial evolution based on the use of indels of conserved proteins and the morphological features of prokaryotic organisms is proposed. In this model, extant archaebacteria and gram-positive bacteria, which have a simple, single-layered cell wall structure, are termed monoderm prokaryotes. They are believed to be descended from the most primitive organisms. Evidence from indels supports the view that the archaebacteria probably evolved from gram-positive bacteria, and I suggest that this evolution occurred in response to antibiotic selection pressures. Evidence is presented that diderm prokaryotes (i.e., gram-negative bacteria), which have a bilayered cell wall, are derived from monoderm prokaryotes. Signature sequences in different proteins provide a means to define a number of different taxa within prokaryotes (namely, low G+C and high G+C gram-positive, Deinococcus-Thermus, cyanobacteria, chlamydia-cytophaga related, and two different groups of Proteobacteria) and to indicate how they evolved from a common ancestor. Based on phylogenetic information from indels in different protein sequences, it is hypothesized that all eukaryotes, including amitochondriate and aplastidic organisms, received major gene contributions from both an archaebacterium and a gram-negative eubacterium. In this model, the ancestral eukaryotic cell is a chimera that resulted from a unique fusion event between the two separate groups of prokaryotes followed by integration of their genomes.

A draft genome of Yersinia pestis from victims of the Black Death

Abstract: Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.

Reliability of a Standardized Mini-Mental State Examination compared with the traditional Mini-Mental State Examination.

Abstract: Objective The objective of this study was to compare the reliability of the Mini-Mental State Examination with that of a new Standardized Mini-Mental State Examination, which has expanded guidelines for administration and scoring. Method The subjects were 32 stable elderly residents of a nursing home and 16 elderly residents of a chronic care hospital unit. Six raters administered the Folstein Mini-Mental State to 22 of these stable elderly subjects, and five raters administered the standardized version to 26 of these subjects. Each subject was tested on three different occasions 1 week apart. Each rater tested 4-6 subjects at the first and third weeks and 4-6 different subjects at the second week. The analytic technique used was one-way analysis of variance to estimate the interrater variance and the intrarater variance. Results The intrarater variance on all occasions was reduced by 86% and the interrater variance was reduced by 76% when the Standardized Mini-Mental State was used; the reductions in variance were significant (p less than 0.003). The intraclass correlation for the Mini-Mental State was 0.69; for the standardized version it was 0.90. It took less time to administer the Standardized Mini-Mental State than the Mini-Mental State. Conclusions The Standardized Mini-Mental State had better reliability than the Mini-Mental State in this study group. Although the improved reliability of the Standardized Mini-Mental State was achieved by reducing measurement noise, this advantage would likely occur in a broad spectrum of patients.

Cuspy No More: How Outflows Affect the Central Dark Matter and Baryon Distribution in Lambda CDM Galaxies

Abstract: We examine the evolution of the inner dark matter (DM) and baryonic density profile of a new sample of simulated field galaxies using fully cosmological, Lambda CDM, high resolution SPH + N-Body simulations. These simulations include explicit H2 and metal cooling, star formation (SF) and supernovae (SNe) driven gas outflows. Starting at high redshift, rapid, repeated gas outflows following bursty SF transfer energy to the DM component and significantly flatten the originally `cuspy' central DM mass profile of galaxies with present day stellar masses in the 10^4.5 -- 10^9.8 Msolar range. At z=0, the central slope of the DM density profile of our galaxies (measured between 0.3 and 0.7 kpc from their centre) is well fitted by rhoDM propto r^alpha with alpha \simeq -0.5 + 0.35 log_10(Mstar/10^8Msolar) where Mstar is the stellar mass of the galaxy and 4 < log_10 Mstar < 9.4. These values imply DM profiles flatter than those obtained in DM--only simulations and in close agreement with those inferred in galaxies from the THINGS and LITTLE THINGS survey. Only in very small halos, where by z=0 star formation has converted less than ~ 0.03% of the original baryon abundance into stars, outflows do not flatten the original cuspy DM profile out to radii resolved by our simulations. The mass (DM and baryonic) measured within the inner 500 pc of each simulated galaxy remains nearly constant over four orders of magnitudes in stellar mass for Mstar 10^9 Msolar. This finding is consistent with estimates for faint Local Group dwarfs and field galaxies. These results address one of the outstanding problems faced by the CDM model, namely the strong discrepancy between the original predictions of cuspy DM profiles and the shallower central DM distribution observed in galaxies.